Rapid and sustained control of Itch and reduction of Th2 bia
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Sezary syndrome is a leukemic variant of cutaneous T cell lymphoma with poor prognosis. With the exception of stem cell transplantation, current treatments for SS are not curative. Rather, they aim at reducing disease burden and improving quality of life. Yet, pruritus the major cause for impaired quality of life in these patients is notoriously difficult to treat. Thus, supportive treatments addressing agonizing pruritus are urgently needed.

A Sezary syndrome patient with stable disease but intractable pruritus was treated with dupilumab in combination with continued extracorporeal photopheresis. Close clinical and immunological monitoring on blood and skin samples from the patient was performed over 44 weeks. In vitro assays with patient's lymphoma cells were performed to address effects of dupilumab on Sezary cell's response to Th2 cytokines.

Clinically, dupilumab treatment induced rapid and sustained reduction of itch and improvement of skin and lymph node involvement. In both blood and skin, a reduction of Th2 bias was observed. Intriguingly, lymphocyte counts and Sezary cells in blood increased and later stabilized under dupilumab treatment. In vitro, dupilumab abrogated the anti-apoptotic and activating effects of Th2 cytokines on Sezary cells.

In this Sezary patient, inhibition of IL-4 and IL-13 signaling was associated with striking clinical benefit in terms of quality of life, pruritus, and use of topical corticosteroids. While safety remains an important concern, this data supports the future exploration of Th2 modulation for supportive care in Sezary Syndrome.

Source: https://onlinelibrary.wiley.com/doi/abs/10.1111/jdv.17001?af=R